HIV Classification: CDC and WHO Staging Systems

Background

HIV disease staging and classification systems are critical tools for tracking and monitoring the HIV epidemic and for providing clinicians and patients with important information about HIV disease stage and clinical management. Two major classification systems currently are in use: the U.S. Centers for Disease Control and Prevention (CDC) classification system and the World Health Organization (WHO) Clinical Staging and Disease Classification System.

The CDC disease staging system (most recently revised in 1993) assesses the severity of HIV disease by CD4 cell counts and by the presence of specific HIV-related conditions. The definition of AIDS includes all HIV-infected individuals with CD4 counts of <200 cells/µL (or CD4 percentage <14%) as well as those with certain HIV-related conditions and symptoms. Although the fine points of the classification system rarely are used in the routine clinical management of HIV-infected patients, a working knowledge of the staging criteria (in particular, the definition of AIDS) is useful in patient care. In addition, the CDC system is used in clinical and epidemiologic research.

In contrast to the CDC system, the WHO Clinical Staging and Disease Classification System (revised in 2007) can be used readily in resource-constrained settings without access to CD4 cell count measurements or other diagnostic and laboratory testing methods. The WHO system classifies HIV disease on the basis of clinical manifestations that can be recognized and treated by clinicians in diverse settings, including resource-constrained settings, and by clinicians with varying levels of HIV expertise and training.

S: Subjective

When a patient presents with a diagnosis of HIV infection, review the patient's history to elicit and document any HIV-related illnesses or symptoms (see chapter Initial History).

O: Objective

Perform a complete physical examination and appropriate laboratory studies (see chapters Initial Physical Examination and Initial and Interim Laboratory and Other Tests).

A: Assessment

Confirm HIV infection and perform staging.

P: Plan

Evaluate symptoms, history, physical examination results, and laboratory results, and make a staging classification according to the CDC or WHO criteria (see below).

CDC Classification System for HIV Infection

The CDC categorization of HIV/AIDS is based on the lowest documented CD4 cell count and on previously diagnosed HIV-related conditions (see Table 1). For example, if a patient had a condition that once met the criteria for category B but now is asymptomatic, the patient would remain in category B. Additionally, categorization is based on specific conditions, as indicated below. Patients in categories A3, B3, and C1-C3 are considered to have AIDS.

Table 1. CDC Classification System for HIV-Infected Adults and Adolescents
CD4 Cell Count CategoriesClinical Categories
A
Asymptomatic, Acute HIV, or PGL
B*
Symptomatic Conditions, not A or C
C#
AIDS-Indicator Conditions

Abbreviations: PGL = persistent generalized lymphadenopathy

(1) ≥500 cells/µLA1B1C1
(2) 200-499 cells/µLA2B2C2
(3) <200 cells/µLA3B3C3

* Category B Symptomatic Conditions

Category B symptomatic conditions are defined as symptomatic conditions occurring in an HIV-infected adolescent or adult that meet at least one of the following criteria:

  • They are attributed to HIV infection or indicate a defect in cell-mediated immunity.
  • They are considered to have a clinical course or management that is complicated by HIV infection.

Examples include, but are not limited to, the following:

  • Bacillary angiomatosis
  • Oropharyngeal candidiasis (thrush)
  • Vulvovaginal candidiasis, persistent or resistant
  • Pelvic inflammatory disease (PID)
  • Cervical dysplasia (moderate or severe)/cervical carcinoma in situ
  • Hairy leukoplakia, oral
  • Herpes zoster (shingles), involving two or more episodes or at least one dermatome
  • Idiopathic thrombocytopenic purpura
  • Constitutional symptoms, such as fever (>38.5°C) or diarrhea lasting >1 month
  • Peripheral neuropathy

# Category C AIDS-Indicator Conditions

  • Bacterial pneumonia, recurrent (two or more episodes in 12 months)
  • Candidiasis of the bronchi, trachea, or lungs
  • Candidiasis, esophageal
  • Cervical carcinoma, invasive, confirmed by biopsy
  • Coccidioidomycosis, disseminated or extrapulmonary
  • Cryptococcosis, extrapulmonary
  • Cryptosporidiosis, chronic intestinal (>1 month in duration)
  • Cytomegalovirus disease (other than liver, spleen, or nodes)
  • Encephalopathy, HIV-related
  • Herpes simplex: chronic ulcers (>1 month in duration), or bronchitis, pneumonitis, or esophagitis
  • Histoplasmosis, disseminated or extrapulmonary
  • Isosporiasis, chronic intestinal (>1-month in duration)
  • Kaposi sarcoma
  • Lymphoma, Burkitt, immunoblastic, or primary central nervous system
  • Mycobacterium avium complex (MAC) or Mycobacterium kansasii, disseminated or extrapulmonary
  • Mycobacterium tuberculosis, pulmonary or extrapulmonary
  • Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
  • Pneumocystis jiroveci (formerly carinii) pneumonia (PCP)
  • Progressive multifocal leukoencephalopathy (PML)
  • Salmonella septicemia, recurrent (nontyphoid)
  • Toxoplasmosis of brain
  • Wasting syndrome caused by HIV (involuntary weight loss >10% of baseline body weight) associated with either chronic diarrhea (two or more loose stools per day for ≥1 month) or chronic weakness and documented fever for ≥1 month

WHO Clinical Staging of HIV/AIDS and Case Definition

The clinical staging and case definition of HIV for resource-constrained settings were developed by the WHO in 1990 and revised in 2007. Staging is based on clinical findings that guide the diagnosis, evaluation, and management of HIV/AIDS, and it does not require a CD4 cell count. This staging system is used in many countries to determine eligibility for antiretroviral therapy, particularly in settings in which CD4 testing is not available. Clinical stages are categorized as 1 through 4, progressing from primary HIV infection to advanced HIV/AIDS (see Table 2). These stages are defined by specific clinical conditions or symptoms. For the purpose of the WHO staging system, adolescents and adults are defined as individuals aged ≥15 years.

Table 2. WHO Clinical Staging of HIV/AIDS for Adults and Adolescents
Clinical StageClinical Conditions or Symptoms
Primary HIV Infection
  • Asymptomatic
  • Acute retroviral syndrome
Clinical Stage 1
  • Asymptomatic
  • Persistent generalized lymphadenopathy
Clinical Stage 2
  • Moderate unexplained weight loss (<10% of presumed or measured body weight)
  • Recurrent respiratory infections (sinusitis, tonsillitis, otitis media, and pharyngitis)
  • Herpes zoster
  • Angular cheilitis
  • Recurrent oral ulceration
  • Papular pruritic eruptions
  • Seborrheic dermatitis
  • Fungal nail infections
Clinical Stage 3
  • Unexplained severe weight loss (>10% of presumed or measured body weight)
  • Unexplained chronic diarrhea for >1 month
  • Unexplained persistent fever for >1 month (>37.6°C, intermittent or constant)
  • Persistent oral candidiasis (thrush)
  • Oral hairy leukoplakia
  • Pulmonary tuberculosis (current)
  • Severe presumed bacterial infections (e.g., pneumonia, empyema, pyomyositis, bone or joint infection, meningitis, bacteremia)
  • Acute necrotizing ulcerative stomatitis, gingivitis, or periodontitis
  • Unexplained anemia (hemoglobin <8 g/dL)
  • Neutropenia (neutrophils <500 cells/µL)
  • Chronic thrombocytopenia (platelets <50,000 cells/µL)
Clinical Stage 4
  • HIV wasting syndrome, as defined by the CDC (see Table 1, above)
  • Pneumocystis pneumonia
  • Recurrent severe bacterial pneumonia
  • Chronic herpes simplex infection (orolabial, genital, or anorectal site for >1 month or visceral herpes at any site)
  • Esophageal candidiasis (or candidiasis of trachea, bronchi, or lungs)
  • Extrapulmonary tuberculosis
  • Kaposi sarcoma
  • Cytomegalovirus infection (retinitis or infection of other organs)
  • Central nervous system toxoplasmosis
  • HIV encephalopathy
  • Cryptococcosis, extrapulmonary (including meningitis)
  • Disseminated nontuberculosis mycobacteria infection
  • Progressive multifocal leukoencephalopathy
  • Candida of the trachea, bronchi, or lungs
  • Chronic cryptosporidiosis (with diarrhea)
  • Chronic isosporiasis
  • Disseminated mycosis (e.g., histoplasmosis, coccidioidomycosis, penicilliosis)
  • Recurrent nontyphoidal Salmonella bacteremia
  • Lymphoma (cerebral or B-cell non-Hodgkin)
  • Invasive cervical carcinoma
  • Atypical disseminated leishmaniasis
  • Symptomatic HIV-associated nephropathy
  • Symptomatic HIV-associated cardiomyopathy
  • Reactivation of American trypanosomiasis (meningoencephalitis or myocarditis)

References

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Abbreviations for Dosing Terminology

BID
twice daily
BIW
twice weekly
IM
intramuscular (injection), intramuscularly
IV
intravenous (injection), intravenously
PO
oral, orally
Q2H, Q4H, etc.
every 2 hours, every 4 hours, etc.
QAM
every morning
QD
once daily
QH
every hour
QHS
every night at bedtime
QID
four times daily
QOD
every other day
QPM
every evening
TID
three times daily
TIW
three times weekly